Pi phenotype was determined and alpha 1 protease inhibitor (alpha 1 Pi) was measured in 871 iron-ore miners examined twice at five years interval. A questionnaire on respiratory symptoms was administered and lung function tests: spirometry (VC, FEV1.0), measurements of the residual volume (RV/TLC) and of the CO diffusion (FuCO), were carried out by the same medical and technical team, using the same apparatus. There were no differences in age, length of employment or smoking habits among the three Pi Phenotype groups: M (90.03%), MS (7.1%), MZ (2.8%). The prevalence of clinical symptoms at the initial survey and the incidence of symptoms between the 2 surveys were not related to Pi Phenotype groups. However a significantly steeper decline of FEV1.0/VC was observed in the alpha 1 Pi partially deficient groups MS and MZ (-3.9%) compared with the non-deficient group (-1.8%). No significant difference was observed for VC, RV/TLC and FuCO. This finding suggests that an intermediate deficiency of alpha 1 Pi may be related to a slight but statistically significant impairment of a lung function in occupational conditions.